Optimized cutaneous delivery of anti-wrinkle dipeptide KT via molecular modification: Preformulation, permeation, and the importance of conjugate chain length.

Introduction: Anti-aging peptides, such as dipeptide KT, are promising rejuvenating agents and have recently received significant attention. However, their hydrophilic nature makes skin absorption therapeutically inadequate. The excessive hydrophilicity of peptides is partially solved by lipoidal conjugates, however, the increased molecular weight due to conjugation creates a new obstacle to skin permeation. Methods: In an attempt to concurrently solve these limitations, here we have studied different short-mid chain fatty acids (C Results: Data showed that the synthesized conjugates substantially outperformed Pal-KT in terms of molecular weight, lipophilicity, melting point, and aqueous solubility. In addition, unlike KT, they all demonstrated amphiphilicity-related features. The maximum and minimum skin permeation were assigned to C Conclusion: Conjugating lower molecular weight fatty acids and optimizing lipophilicity can enhance molecular properties, skin absorption, and the ability to form supramolecular structures. This, in turn, leads to the development of superior anti-wrinkle products and formulations.